Memory consolidation and forgetting are both critical for individuals’ survival and development, while abnormality in the two processes leads to various neuropsychiatric diseases, such as Alzheimer’s disease, post-traumatic stress disorder and anxiety. Recently, Lin Lu’s group from Peking University Sixth Hospital reported novel molecular mechanisms of memory enhancement and erasure in Neuropsychopharmacology and The Journal of Neuroscience.

In the paper published in the Neuropsychopharmacology, Lin Lu’s group investigated whether overexpression of PKMzeta enhances the formation of auditory fear memory in rats. Overexpression of PKMzeta in the prelimbic cortex (PrL) enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas PKMzeta overexpression in the infralimbic cortex had no effect on either short-term or long-term fear memory. Overexpression of PKMzeta in the PrL did not affect anxiety-like behavior or locomotor activity. They also found that PKMzeta overexpression potentiated fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL. These results demonstrate that the overexpression of PKMzeta in the PrL may be selectively involved in the enhancement of fear memory, which extends our understanding of the role of PKMzeta in learning and memory and related neurological disorders.

In the paper published in The Journal of Neuroscience, Lin Lu’s group investigated the effect of novelty on long-lasting persistence of extinction memory. They found that exposure to a novel environment but not a familiar one 1 h before or after extinction enhanced extinction long-term memory (LTM) and reduced fear reinstatement. Inhibition of the beta-adrenergic receptor (beta-AR) –PKA-CREB pathway or the glucocorticoid receptor (GR)-ERK1/2 pathway in the CA1 area of the dorsal hippocampus before novelty exposure blocked the effect of novelty on extinction memory, while inhibition of GR-Erk1/2 but not beta-AR–PKA-CREB before extinction disrupted the formation of extinction LTM, suggesting that hippocampal GR and Erk1/2 play critical roles in this process. These results indicate that hippocampal beta-AR- and GR-dependent pathways are involved in the behavioral tagging of extinction, and suggests that enhancing behavioral tagging of extinction may improve the efficacy of exposure therapy for post-traumatic stress disorder or anxiety-related disorders.

Yan-Xue Xue, Zhen-Zhen Zhu, Hai-Bin Han, Jian-Feng Liu, Shi-Qiu Meng, Chen Chen, Jian-Li Yang, Ping Wu, Lin Lu (2015). Overexpression of protein kinase Mζ in the prelimbic cortex enhances the formation of long-term fear memory.  Neuropsychopharmacology . doi: 10.1038/npp.2015.56. [Epub ahead of print]

Jian-Feng Liu, Chang Yang, Jia-Hui Deng, Wei Yan, Hui-Min Wang, Yi-Xiao Luo, Hai-Shui Shi, Shi-Qiu Meng, Bai-Sheng Chai, Qin Fang, Ning Chai, Yan-Xue Xue, Jia Sun, Chen Chen, Xue-Yi Wang, Ji-Shi Wang, Lin Lu (2015). Role of hippocampal β-adrenergic and glucocorticoid receptors in the novelty-induced enhancement of fear extinction.  J Neurosci . doi: 10.1523/JNEUROSCI.0005-15.2015.